Abstract
Chronic rejection limits the survival after lung transplantation. Probably, not only the immune system is involved but also the lung integrity and its structural cells. A range of insults towards the bronchial epithelium can be responsible for loss of airway integrity resulting in 'Obliterative Bronchiolitis' (OB). We hypothesize that immunosuppressives affect airway integrity.
A biculture of lung bronchial epithelial cells (16HBE) and human lung microvascular endothelial cells (HLMVEC) were exposed to immunosuppressives (serum through levels) for 24h, 5 and 10 days at the endothelial side. Cytotoxicity was measured using a WST-1 assay after 1 and 5 days. Trans epithelial electrical resistance (TEER) was measured 1, 6 and 10 days after addition of mycophenolate mofetil (MMF) or a combination therapy of MMF, tacrolimus and dexamethasone (DEX) or azathioprine, cyclosporin and DEX. Cytotoxicity and TEER were measured at the epithelial side.
MMF alone and in combination with tacrolimus and DEX was not toxic for the epithelial cells after 24h but was after chronic exposure of 5 days. TEER, however, significantly decreased after 24h. Cells exposed to MMF for 24h could recover their TEER after a few days when MMF was replaced by fresh medium. The combination of azathioprine, cyclosporin and DEX was not toxic for the cells and TEER did not decrease.
MMF alone and in combination with tacrolimus and DEX was not toxic after 24 hours but TEER dropped, probably by destruction of the tight junctions of the epithelial cells. Loss of the tight junctions between adjacent epithelial cells by immunosuppresives could result in loss of airway integrity and might be a trigger for the excessive repair mechanism that eventually leads to OB lesions.
- Copyright ©ERS 2015
